The objective of this proposal is the synthesis and utilization of functionalized molecular probes specific for the imidazoline/guanidinium receptive site (IGRS), a potential important receptor involved in metabolic and cardiovascular regulation. IGRS-selective molecules will be chemically modified to generate 1) a radioiodinated ligand for cell-localization of IGRS and 2) a radioiodinated photoaffinity adduct for identification and structural characterization of the receptor's hormone binding subunit. Novel derivatives will also be synthesized for construction of an affinity matrix for protein purification. Imidazoline and guanidinium compounds such as clonidine and guanabenz elicit a wide variety of responses in both the central nervous system and peripheral tissues. Although many of these cellular effects are mediated by alpha2-adrenergic receptors, both functional and radioligand binding studies indicate that this class of pharmacologically active compounds interact with a cellular protein (IGRS) distinct from the alpha2-adrenergic receptor. Indeed, IGRS does not recognize catecholamines or other known neurotransmitters but does recognize an endogenous clonidine displacing substance purified from brain suggesting the existence of a previously unidentified hormonal/neurotransmitter-receptor system. Detailed analysis of this system and IGRS is limited by the lack of high-specific activity probes specific for the receptor protein.